Schmidt ? Project Summary Radical species play important roles in biological systems linked not only to dysfunctional cell proliferation and other disease pathways, but also in essential healthy processes necessary for life. Understanding the reactivity profiles of open-shell carbon, oxygen, sulfur, and other heteroatomic-centered radical intermediates is crucial to understanding how these processes occur and to propose reasonable mechanisms for currently ill-defined pathways. Studying and understanding reactivity profiles of radical intermediates can also result in the development of new synthetic methodologies with the potential to streamline and make the synthesis of existing pharmaceuticals more efficient and provide access to the next generation of therapeutics and tools for imaging, diagnosis, treatment, and prevention. This proposal is built on the prior and concurrent efforts of the PI?s research group using phosphorous-based reagents to unmask carbon and heteroatom-centered radicals from untraditional precursors. This general platform has achieved the regioselective construction of C-N bonds which are present in a substantial portion of FDA approve pharmaceuticals and are often involved in the mode of biological activity. These radical-mediated approaches leverage the favorable thermodynamics of atom-transfer processes to achieve new bond formations from common chemical functionalities. Future studies will continue to explore the potential of this general platform by investigating the ability of other common functional groups to be analogously unmasked to achieve new bond formations. We anticipate that this work may lead to new strategies in complex molecule construction for use in the preparation of new molecular therapeutics and tools in chemical biology.